Cytotoxicity of new alkylamino- and phenylamino-containing polyfluorinated derivatives of 1,4-naphthoquinone

Fluorinated derivatives of 1,4-naphthoquinone are highly potent inhibitors of Cdc25A and Cdc25 phosphatases and growth of tumor cells. Five new N-substituted polyfluorinated derivatives of 2-amino-1,4-naphthoquinone were synthesized and their mutagenic and antioxidant properties in Salmonella cells, as well as cytotoxicity in human myeloma (RPMI 8226), human mammary adenocarcinoma (MCF-7), mouse fibroblasts (LMTK) and primary mouse fibroblast cells (PMF) were studied. 2-tert-Butylamino-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (1) inhibited the growth of normal control and tumor cells at the same concentration. Three compounds: 2-diethylamino-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (2), 2-ethylamino-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (3), 2-phenylamino-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (4) exhibited a 50% decrease in the growth of cancer cells at low and comparable concentrations (2.4–8.6 μM) while being remarkably less cytotoxic toward normal LMTK and PMF cells. Quinones (1)–(4), but not 2-phenylamino-3-methyl-5,6,7,8-tetrafluoro-1,4-naphthoquinone (5), efficiently suppressed spontaneous mutagenesis in Salmonella cells, while all compounds 1–5 decreased the mutagenic effect of H2O2 on bacterial cells. Their possible perspectives as anticancer drugs are shortly discussed.

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